Opioid Prescribing and Outcomes in Patients With Sickle Cell Disease Post-2016 CDC Guideline

Abstract

Importance: Although the intention of the 2016 US Centers for Disease Control and Prevention (CDC) Guideline for Prescribing Opioids for Chronic Pain was not to limit pain treatment for patients with sickle cell disease (SCD), clinicians and patients have recognized the possibility that the guideline may have altered outcomes for this population. However, the outcomes of the 2016 guideline for this patient population are unknown.

Objective: To examine changes in opioid prescribing patterns and health outcomes among patients with SCD before and after the release of the 2016 CDC guideline.

Design, setting, and participants: This retrospective cohort study conducted interrupted time series analysis of claims data from the Merative MarketScan Commercial Database from January 1, 2011, to December 31, 2019. In this population-based study in the US, individuals with SCD who were at least 1 year of age, had no cancer diagnosis, and had pharmacy coverage for the month of measurement were included. The data were analyzed from January 2021 to November 2023.

Exposure: The CDC Guideline for Prescribing Opioids for Chronic Pain released in March 2016.

Main outcomes and measures: The main variables measured in this study included the practice of opioid prescribing among patients with SCD (ie, rate of opioid prescriptions dispensed, mean number of days supplied, mean total morphine milligram equivalents [MME] per patient, and mean daily MME per opioid prescription) and pain-related health outcomes (rates of emergency department visits related to vaso-occlusive crises [VOC] and hospitalizations related to VOC).

Results: The cohort included 14 979 patients with SCD (mean [SD] age, 25.9 [16.9] years; 8520 [56.9%] female). Compared with the preguideline trends, the following changes were observed after the guideline was released: significant decreases in the coefficient for change in slope of the opioid dispensing rate (-0.29 [95% CI, -0.39 to -0.20] prescriptions per 100 person-month; P < .001), the number of days supplied per prescription (-0.05 [95% CI, -0.06 to -0.04] days per prescription-month; P < .001), and opioid dosage (-141.0 [95% CI, -219.5 to -62.5] MME per person-month; P = .001; -10.1 [95% CI, -14.6 to -5.6] MME/prescription-month; P < .001). Conversely, a significant increase in VOC-related hospitalizations occurred after the guideline release (0.16 [95% CI, 0.07-0.25] hospitalizations per 100 person-month; P = .001). These changes were observed to a greater extent among adult patients, but pediatric patients experienced similar changes in several measures, even though the guideline focused exclusively on adult patients.

Conclusions and relevance: This retrospective cohort study showed that the 2016 CDC guideline may have had unintended negative outcomes on the patient population living with SCD.

Figure 1.. Opioid Prescription Patterns Among Individuals With Sickle Cell Disease Before and After 2016 CDC Guideline

Dashed blue vertical lines represent the month of the Centers for Disease Control and Prevention (CDC) guideline implementation (March 2016). The blue dots and solid black lines represent the actual values and fitted lines, respectively. The change in slope (ie, rate of decrease per month) from before to after the CDC guideline release was statistically significant in panels B, C, and D (B, P < .001; C, P = .001; D, P < .001). MME indicates morphine milligram equivalent. ^aThe change in slope did not reach statistical significance (P = .56).

Figure 2.. Pain-Related Health Outcomes Among Individuals With Sickle Cell Disease Before and After 2016 CDC Guideline

Dashed blue vertical lines represent the month of the Centers for Disease Control and Prevention (CDC) guideline implementation (March 2016). The blue dots and solid black lines represent the actual values and fitted lines, respectively. The change in slope (ie, rate of decrease per month) from before to after the CDC guideline release was statistically significant (A, P < .001; B, P < .001). ED indicates emergency department; VOC, vaso-occlusive crises.

Figure 3.. Opioid Prescription Fills and Pain-Related Health Outcomes Among Pediatric and Adult Patients With Sickle Cell Disease Before and After 2016 CDC Guideline

Dashed blue vertical lines represent the month of the Centers for Disease Control and Prevention (CDC) guideline implementation (March 2016). The blue dots and solid black lines represent the actual values and fitted lines, respectively, for adult patients. The orange dots and dashed black lines represent the actual values and fitted lines, respectively, for pediatric patients. The top slope values in each panel apply to adults; the bottom slope values in each panel apply to children, as noted in panel A. The change in slope (ie, rate of decrease per month) from before to after the CDC guideline release was statistically significant in adults in panels B to F, as well as in children in panels B, C, and F (B, adults: P < .001; children: P < .001; C, adults: P < .001; children: P = .02; D, adults: P < .001; E, adults: P < .001; F, adults: P < .001; children: P = .01). ED indicates emergency department; MME, morphine milligram equivalent; VOC, vaso-occlusive crises. ^aThe change in slope did not reach statistical significance (A, adults: P = .44; children: P = .50; D, children: P = .10; E, children: P = .35).